PB1907: CLINICAL VALUE OF DETECTING ABL KINASE MUTATIONS IN CHRONIC MYELOID LEUKEMIA BASED ON HIGH THROUGHPUT SEQUENCING TECHNOLOGY
Authors: Z. LING, L. XIAODONG, W. XIANWEI, Z. ZHE, W. LINLIN, L. YANGWEI
Journal: HemaSphere (2022)

Background: Tyrosine kinase inhibitor (TKI) is effective in the treatment of chronic myeloid leukemia (CML), but about 20% ~ 30% of patients still have TKI resistance, which is mainly due to the drug resistance mutation in ABL kinase region.In order to further optimize TKI treatment and achieve the best treatment response, sensitive and accurate detection of ABL kinase region mutation has important clinical value.Sanger sequencing is the gold standard for detecting mutations in ABL kinase region, but its sensitivity is low, the proportion of mutations that are easy to be missed is less than 15 ~ 20%, and it is a qualitative detection, which can not distinguish the mutated clone structure.In recent years, high-throughput sequencing technology has gradually become a routine clinical diagnostic method for blood tumors. Its sensitivity to detect mutations can reach 1%, and the clonal structure of mutations can be analyzed according to the variant allele frequency (VAF value) of mutation sites to further clarify the clonal structure of mutations.This study compared and analyzed the efficiency of high-throughput sequencing and Sanger sequencing in detecting ABL kinase region mutations, further clarified the clinical value of high-throughput sequencing in detecting low proportion mutations and multipoint mutations in ABL kinase region, and provided basis for TKI precision treatment. Aims: To compare the efficacy and clinical impact of high throughput sequencing and SS (Sanger sequencing) in detecting ABL kinase domain mutations. Methods: A total of 198 samples of 147 CML patients from July 2017 to March 2021 in Henan cancer hospital were collected and sequenced by high throughput sequencing and SS to detect the mutation of ABL kinase domain, and relevant clinical data were collected for comparative analysis. Results: The proportion of mutations and ≥ 2 mutations detected by high throughput sequencing was significantly higher than that by SS (P=0.046). Of the 22 cases with ≥ 2 mutations, 5 (23%) were found to have compound mutations. In 198 samples, 25 (13%) were low proportion mutations, 33 (17%) were high proportion mutations and 10 (5%) were mixed high and low proportion mutations. In the analysis of related clinical factors, the proportion of mutation detection and the proportion of low mutation in the optimal, failure and warning response were gradually increased (mutation proportion, P=0.016; P=0.038); The proportion of mutation with additional chromosomal abnormalities was also significantly increased (P=0.009).The mutation rate of patients receiving first-line and second-line treatment was significantly lower than that of patients receiving third-line and fourth line treatment (P=0.006).According to the VAF value analysis of mutation sites, it is helpful to visually evaluate the clonal evolution status of TKI-resistance in CML. Summary/Conclusion: High throughput sequencing is more sensitive and accurate than Sanger sequence in mutation detection, which is helpful for accurate and visual evaluation of TKI treatment response and optimization of treatment strategy for CML.